Interferon is a glycoprotein derived from most of the cells having a nucleus, and has antiviral property by inhibiting proliferation of viruses. Interferon elicits a series of intracellular responses and immunoregulatory responses by binding to a specific receptor on the cell membrane of the cell surface. The intracellular responses may include induction of the activation of specific enzymes, etc., and the immunoregulatory responses may include enhancing the phagocytosis activity of macrophages, increasing the cytotoxicity of lymphocytes against target cells, and inhibiting proliferation of viruses in virus-infected cells, etc.
Interferons are classified into type 1 and type 2 based on the physiochemical and functional properties. Type 1 interferons include interferon-α, -β, -τ, and -ω; and type 2 interferons include interferon-γ. Among them, interferon-β is a protein of a single chain, which has a molecular weight of approximately 20 kDa, contains a sugar of about 20%, and is composed of 166 amino acids.
Currently, recombinant interferon-β is used along with interferon-α as a therapeutic agent for disorders caused by various viruses such as hepatitis B virus and hepatitis C virus. It was reported that the recombinant interferon-β can be used as an immune adjuvant for inhibiting the recurrence of papilloma virus infection (Gross G. et al., Dermatology, 1998; 196(3):330-4).
Recently, researches have been made to enhance immune responses and treat various disorders by using an RNA oligonucleotide. U.S. Patent Application Publication No. 2012/0288476 discloses that an uncapped oligonucleotide having a phosphate group at the 5′-end can increase the expression of type 1 interferon, interleukin-18, and interleukin-1β, etc, suggesting its use as an antiviral agent.
In addition, U.S. Patent Application Publication No. 2012/0121551 discloses that an RNA consisting of four nucleotides can promote immune responses by inducing the activation of interferon-α, suggesting its use for treating a disorder.
The RNAs mentioned above have a common feature that they all have a triphosphate group at the 5′-end. It has been known in the art that an uncapped RNA which has a triphosphate group at the 5′-end can activate the expression of interferon by binding to intracellular retinoic acid-inducible gene-I (RIG-I) protein.